Trends, Predictors and Outcomes of Ischemic Stroke Among Patients Hospitalized with Takotsubo Cardiomyopathy.

OBJECTIVES: This study assessed the temporal trends in the incidence of ischemic stroke among patients hospitalized with takotsubo cardiomyopathy (TCM) stratified by the subtypes of ischemic stroke (cardioembolic versus thrombotic). Predictors of each stroke subtype, the association with atrial fibrillation (AF), the occurrence of ventricular fibrillation/ventricular tachycardia (VF/VT), cardiogenic shock (CS), in-hospital mortality, length of stay (LOS), and total healthcare cost were also assessed. BACKGROUND: Ischemic stroke in TCM is thought to be primarily cardioembolic from left ventricular mural thromboembolism. Limited data are available on the incidence of thrombotic ischemic stroke in TCM. MATERIALS AND METHODS: We identified 27,970 patients hospitalized with the primary diagnosis of TCM from the 2008 to 2017 National Inpatient Sample, of which 751 (3%) developed ischemic stroke. Of those with ischemic stroke, 571 (76%) had thrombotic stroke while 180 (24%) had cardioembolic stroke. Cochrane armitage test was used to assess the incidence of thrombotic and cardioembolic strokes and multivariate regression was used to identify risk factors associated with each stroke subtype. We compared the incidence of AF, VF/VT, CS, LOS, in-hospital mortality and total cost between hospitalized patients with TCM alone to those with cardioembolic and thrombotic strokes. RESULTS: From 2008 - 2017, the incidence of thrombotic stroke (4.7%-9.5% (p< 0.0001) increased while it was unchanged for cardioembolic stroke (0.5%-0.7% P=0.5). In the multivariate regression, peripheral artery disease, prior history of stroke, and hyperlipidemia were significantly associated with thrombotic stroke, while CS, AF, and Asian race (compared to White race) were associated with cardioembolic stroke. Both cardioembolic and thrombotic strokes were associated with higher odds of IHM, AF, CS, longer LOS and increased cost. Trends in in-hospital mortality and the utilization of thrombolysis, cerebral angiography, and mechanical thrombectomy among patients with TCM and ischemic stroke were unchanged from 2008 to 2017. CONCLUSION: Among patients with TCM and ischemic stroke, thrombotic stroke was more common compared to cardioembolic stroke. Ischemic stroke was associated with poorer outcomes, including higher in-hospital mortality and increased healthcare resource utilization in TCM.

Coexistence of acute takotsubo syndrome and acute coronary syndrome.

BACKGROUND: Takotsubo syndrome (TS) is an acute cardiac condition with presentation indistinguishable from acute coronary syndrome (ACS), and mechanism independent of epicardial coronary obstruction. Acute coronary artery plaque rupture/occlusion is not expected in TS. Nonetheless, the physiologic stress of ACS might itself trigger TS, leading to coexistence of both conditions, and diagnostic uncertainty. METHODS: From 2011 to 2014, we encountered 137 consecutive patients with typical TS (without acute coronary plaque rupture/occlusion). During this time, among a population of 3,506 consecutive ACS patients, nine (0.3%) presented with features of both ACS and TS, that is, acute onset, troponin elevation, acute plaque rupture/occlusion, and reversible LV ballooning not corresponding to culprit coronary distribution. RESULTS: The nine patients (seven female) with TS-ACS coexistence, average age 70 ± 13 years, presented with chest pain (n = 6), nausea/vomiting (n = 2), or cardiac arrest (n = 1), ST-elevation (n = 5), all with troponin elevation (peak 1.3 ± 1.2 ng/ml). Each had single vessel coronary disease; right coronary (n = 3), circumflex (n = 3), mid-LAD (n = 2), ramus intermedius (n = 1), with percutaneous coronary intervention in seven patients (78%). Initial ejection fraction was 26 ± 7%, with apical ballooning in eight patients and mid-LV ballooning in one patient. Each patient had LV ballooning resolution and ejection fraction normalization to 57 ± 3%, hospital survival was 89%. CONCLUSIONS: Among patients with ACS, a subset have evidence of coexisting TS, findings which further expand the clinical profile of both conditions, raising the possibility that ACS itself may trigger TS.

The GRACE Scale in the Prognosis of Patients with Takotsubo Syndrome.

BACKGROUND: The prognosis of Takotsubo syndrome (TTS) is comparable to that of the non-ST-elevation myocardial infarction (NSTEMI). The GRACE scale is used to assess the risk of premature and long-term mortality in patients with NSTEMI in order to select the most favorable treatment strategy. METHODS: 101 patients with TTS hospitalized in four centers of invasive cardiology in Podlaskie Voivodeship during the period 2008-2012 were included in the study. The patients were divided into two groups: I-52 patients (GRACE ≤ 140 points) and II-49 patients (GRACE > 140 points). RESULTS: The mean GRACE score in the study group was 138.66. The in-hospital stay of Takotsubo in the patients with higher GRACE scores was associated with higher incidence of pneumonia (36.7% vs 7.69%, p=0.0004), rhythm abnormalities (17.3% vs 3.85%, p=0.026), and serious complications (cardiogenic shock, pulmonary edema, and sudden cardiac arrest) (30.6% vs 5.77%, p=0.001). The mean observation period was 7.2 years. A significantly higher risk of 6-month (18.37% vs 3.85%, p=0.019), 1-year (22.45 vs 3.85%, p=0.005), 3-year (40.82 vs 3.85%, p < 0.0001), 5-year (42.86% vs 3.85%, p < 0.0001), and 7-year mortalities (53.06% vs 9.62%, p < 0.0001) was observed in the group of patients with a GRACE score ≥140. At multivariate analysis including low BMI, low eGFR, and a higher GRACE score, all these factors were independent predictor of death (p=0.042; p=0.010; p=0.041). The ROC curve presents the discriminatory scores of the GRACE scale for the follow-up prognostication. The area under ROC curve (AUC) for the GRACE scale was 0.805 (95% CI: 0.718-0.892, p < 0.0001), with a cut-off value of 153 points, sensitivity of 74%, and specificity of 77% for TTS. CONCLUSION: The GRACE scale is highly valuable for the prognostication of death risk in patients with TTS in the early and long-term observation.

Systemic Inflammatory Response Syndrome Is a Major Determinant of Cardiovascular Outcome in Takotsubo Syndrome.

BACKGROUND: Recent insights have emphasized the importance of inflammatory response in takotsubo syndrome (TTS). We sought to evaluate the predictors of systemic inflammatory response syndrome (SIRS) and its impact on cardiovascular mortality after TTS.Methods and Results:The 215 TTS patients were retrospectively included between September 2008 and January 2018. SIRS was diagnosed in 96 patients (44.7%). They had lower left ventricular ejection fraction (LVEF) on admission (34.5% vs. 41.9%; P<0.001) and higher peak brain natriuretic peptide and troponin. At a median follow-up of 518 days, SIRS was associated with increased in-hospital mortality (14.6% vs. 5.0%; P=0.019), overall mortality (29.4% vs. 10.8%; P=0.002), and cardiovascular mortality (10.6% vs. 2.1%; P=0.026). A history of cancer (OR, 3.36; 95% CI: 1.54-7.31; P=0.002) and LVEF <40% at admission (OR, 2.31; 95% CI: 1.16-4.58; P=0.017) were identified as independent predictors of SIRS. On multivariate Cox regression analysis, SIRS (HR, 12.8; 95% CI: 1.58-104; P=0.017), age (HR, 1.09; 95% CI: 1.02-1.16; P=0.01), and LVEF <40% at discharge (HR, 9.88; 95% CI: 2.54-38.4; P=0.001) were independent predictors of cardiovascular death. CONCLUSIONS: SIRS was found in a large proportion of TTS patients and was associated with enhanced myocardial damage and adverse outcome in the acute phase. At long-term follow-up, SIRS remained an independent factor of cardiovascular death.

Incremental "Therapeutic" Myocardial Exposure to Catecholamines: Incidence and Impact in Takotsubo Syndrome.

BACKGROUND: Although Takotsubo syndrome (TS) was once considered to be rare and largely benign, it is now recognized to represent a major cause of cardiac morbidity and mortality, especially in ageing women. The biochemical precipitant of attacks of TS is an increase in catecholamine concentrations within the myocardium, engendering inflammatory activation via biased post-receptor signalling at myocardial ß2-adrenoceptor level. Cases of TS have been reported in patients treated with catecholamines, and with antidepressants which limit catecholamine re-uptake. In the current investigation, we sought to delineate the extent and potential impact of this "iatrogenic" form of TS. METHODS/RESULTS: Patients' data from a regional registry of 301 consecutive cases of TS were evaluated after exclusion of patients (n = 20) in whom TS had occurred in association with life threatening extracardiac disease states. A total of 55 (18%) of patients were identified as having antecedent exposure to potentially "iatrogenic" agents (tricyclic antidepressants in 24 cases, ß2-adrenoceptor agonists in 15). Demographics, including proportion of male patients, did not differ significantly between patients with and without "iatrogenic" TS, but plasma concentrations of the catecholamine metabolite normetanephrine tended to be greater (median 1149 pmol/L vs 938 pmol/L; p = 0.03). Long-term survival (median follow-up 3 years) was marginally (p = 0.13) worse for patients with "iatrogenic" TS. CONCLUSION: Potentially iatrogenic precipitation of TS attacks (via iatrogenic elevation of catecholamine levels and ß2-adrenoceptor stimulation) is common, associated with greater elevation of plasma normetanephrine concentrations, and also with a trend towards increased long-term mortality when compared to the remainder of TS patients.

Takotsubo syndrome: an overview of pathophysiology, diagnosis and treatment with emphasis on cancer patients.

Takotsubo syndrome is a disease of great clinical importance that remains underdiagnosed. It is a form of acute heart failure characterized by a transient wall motion abnormality of the left ventricular apex typically triggered by emotional or physical stress. Takotsubo syndrome is commonly associated with cancer and results in poor outcomes. Therefore, early recognition and prompt therapy are essential to improve prognosis. The aim of this manuscript is to review the consequences of the association between cancer and Takotsubo to summarize the available evidence to guide physicians to improve the management of these patients.

Impact of T-inversion on the outcome of Takotsubo syndrome as compared to acute coronary syndrome.

BACKGROUND: Previous studies revealed that patients with Takotsubo syndrome (TTS) have a higher mortality rate than the general population and a comparable mortality to acute coronary syndrome (ACS). Repolarisation abnormalities, namely T-wave amplitude, may provide incremental prognostic information, in addition to traditional risk factors in ACS. This study was performed to determine the short- and long-term prognostic impact of inverted T-waves in TTS patients, as compared to ACS patients. METHODS AND RESULTS: Our institutional database constituted a collective of 138 patients diagnosed with TTS from 2003 to 2017, as well as 532 patients suffering from ACS. Patients with TTS or with ACS (n = 138 per group) were matched for age and sex and assessed retrospectively and prospectively and divided into two groups, TTS with inverted T-waves (n = 123) and ACS with inverted T-waves (n = 80). In-hospital complications such as respiratory failure with the need of respiratory support (60.2% vs 6.3%; P < 0.01), thromboembolic events (13.8% vs 2.5%; P < 0.01) and cardiogenic shock (18.9% vs 8.8%; P = 0.05) were significantly more presented in TTS as compared to ACS patients. Among cardiovascular risk factors diabetes mellitus (23.6% vs 45.0%; P < 0.01) and arterial hypertension (57.7% vs 78.8%; P < 0.01) were more presented in ACS patients as compared to TTS patients. Short-term mortality was similar, however the long-term mortality of 5 years was significantly higher in the TTS group (25.2% vs 7.5%; P < 0.01). In univariate analysis were male gender, EF < 35%, GFR < 60 mL/min, cardiogenic shock, inotropic drugs and history of cancer predictors of 5-year mortality. The multivariate analysis showed only male gender (HR 2.7, 95% CI 1.1-6.5; P = 0.02), GFR < 60 mL/min (HR 2.8, 95% CI 1.2-6.0; P = 0.01) and history of cancer (HR 3.6, 95% CI 1.4-9.3; P < 0.01) as independent predictors of 5-year mortality. CONCLUSION: Rates of long-term mortality were significantly higher in TTS patients showing inverted T-waves compared with patients diagnosed with ACS with inverted T-waves. However, T-inversion was not an independent predictor of 5-year mortality in the multivariate analysis.

In-hospital Takotsubo syndrome versus in-hospital acute myocardial infarction among patients admitted for non-cardiac diseases: a nationwide inpatient database study.

Takotsubo syndrome (TTS) and acute myocardial infarction (AMI) occasionally occur during hospitalization for non-cardiac diseases. However, no study has compared the clinical characteristics between in-hospital TTS and AMI. Using the Diagnosis Procedure Combination database in Japan between 2010 and 2014, we retrospectively identified eligible inpatients who were admitted for non-cardiac diseases and developed TTS (n = 230) or AMI (n = 611) as an early in-hospital complication diagnosed by coronary angiography within 7 days after admission. We examined factors associated with developing in-hospital TTS or AMI using multivariable logistic regression. We also compared 30-day and overall in-hospital mortality between patients with TTS and AMI using 1:1 propensity score matching. Despite similar age (72.7 ± 12.4 vs. 72.8 ± 10.4 years), patients with TTS were more often female (63.5 vs. 32.9%) and underweight (24.8 vs. 14.1%) and were more likely to have had impaired activities of daily living (ADL) and impaired consciousness than those with AMI. Multivariable logistic regression analysis showed that female sex [adjusted odds ratio: 4.16 (95% confidence interval: 2.73-6.34)], impaired ADL [2.33 (1.18-4.60)], chronic pulmonary disease [3.33 (1.49-7.44)], and pneumonia [3.00 (1.81-4.98)] were associated with developing TTS relative to AMI, while overweight status, aortic disease, cerebrovascular disease, peripheral arterial disease, and dyslipidemia were associated with developing AMI relative to TTS. Propensity score-matched analysis (189 pairs) showed that 30-day in-hospital mortality was not significantly different between patients with TTS and AMI (15.3 vs. 19.0%, p = 0.41), but overall in-hospital mortality was significantly lower in patients with TTS than in those with AMI (19.6 vs. 29.1%, p = 0.041). This study suggests that although in-hospital TTS and in-hospital AMI are similarly likely to occur in older patients, in-hospital TTS is more likely to occur in female patients with impaired ADL and/or respiratory disease and carries a similar 30-day mortality risk but a lower overall in-hospital mortality risk compared with in-hospital AMI. Our results indicate the importance of differentiating TTS from AMI in hospital settings.

Importance of sympathetic nervous system activity during left ventricular functional recovery and its association with in-hospital complications in Takotsubo syndrome.

The relationship between activation of the sympathetic nervous system (SNS) and improvement of left ventricular (LV) function and how this correlates with clinical outcomes are not fully explored in Takotsubo syndrome (TS). The purpose of this study is to evaluate the relationship between activation of the SNS and LV function improvement and how this correlates with clinical outcomes in TS. Patients with TS were retrospectively identified. Patients were divided into two groups according to the timing of LV function improvement: < 1 month (S group) and ≥ 1 month (L group). Activation of the SNS was assessed by plasma catecholamine measurement and Iodine-123 meta-iodobenzylguanidine (I123-MIBG) scintigraphy. In-hospital complications included heart failure, cardiogenic shock, the use of invasive or noninvasive ventilation, life-threatening arrhythmia, cerebrovascular event and all-cause death. A total of 90 patients with TS were enrolled. Of these, 39 patients were in the S group and 51 in the L group. There were no significant differences between the two groups in clinical demographics. The L group was characterized by enhanced SNS activation, including higher levels of catecholamines and lower late heart-mediastinum ratio followed by higher washout rate in I123-MIBG scintigraphy, compared with the S group. In-hospital complications were increased in the L group (56% vs. 33.3%, p = 0.03), including higher rates of heart failure (45% vs. 23%, p = 0.03) and in-hospital death (8.0% vs. 0%, p = 0.03). In patients with TS, high activity of the SNS was observed in patients with delayed LV function recovery, which was associated with in-hospital adverse outcomes.

Protective effect of acquired long QT syndrome in Takotsubo syndrome.

BACKGROUND: Clinical variables that predict long-term mortality and recurrence of Takotsubo syndrome (TTS) are not completely understood as the role of acquired corrected QT interval (QTc) prolongation. AIM: To detect the prevalence of QTc interval prolongation in patients with TTS and to evaluate its long-term prognostic impact. METHODS: QTc intervals were analysed in 105 patients presenting with symptoms of TTS. These patients were included in an ongoing retrospective cohort database. The cohort was subsequently subdivided into two groups based on the presence (long QT (LQT) group, n = 73, 69.52%) or absence (non-long QT (non-LQT) group, n = 32, 30.43%) of QTc interval prolongation. Patients were followed up over a mean period of 4.2 years. The rate of life-threatening arrhythmia during the first 30 days in the LQT group was comparable with the non-LQT group (10.9 vs 12.5%), whereas in-hospital mortality and 30-day mortality occurred less frequently in the LQT group (2.7 vs 18.75%, P < 0.01). RESULTS: During this time span, 17 (23.3%) patients with acquired LQT syndrome died, whereas 14 (43.7%) patients with non-LQT duration died. Kaplan-Meier survival rates were significantly higher in the LQT group than those in the non-LQT group (Log-rank-test, P = 0.02). On multivariate analysis, the QTc interval was an independent negative predictor of all-cause mortality (P = 0.02). CONCLUSION: The QTc interval at admission is an independent negative predictor of long-term adverse outcome in patients with TTS.

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

BACKGROUND: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

Clinical outcomes associated with catecholamine use in patients diagnosed with Takotsubo cardiomyopathy.

BACKGROUND: Recent hypotheses have suggested the pathophysiological role of catecholamines in the evolution of the Takotsubo syndrome (TTS). The extent of cardiac and circulatory compromise dictates the use of some form of supportive therapy. This study was designed to investigate the clinical outcomes associated with catecholamine use in TTS patients. METHODS: Our institutional database constituted a collective of 114 patients diagnosed with TTS between 2003 and 2015. The study-patients were subsequently classified into two groups based on the need for catecholamine support during hospital stay (catecholamine group n = 93; 81%, non-catecholamine group = 21; 19%). The primary end-point of our study was all-cause mortality. RESULTS: Patients receiving catecholamine support showed higher grades of circulatory and cardiac compromise (left ventricular ejection fraction (LVEF) 39.6% vs. 32.7%, p-value < 0.01) and the course of disease was often complicated by the occurrence of different TTS-associated complications. The in-hospital mortality (3.2% vs. 28.5%, p < 0.01), 30-day mortality (17.2% vs. 51.4%, p < 0.01) as well as long-term mortality (38.7% vs. 80.9%, p < 0.01) was significantly higher in the group of patients receiving catecholamine support. A multivariate Cox regression analysis attributed EF ≤ 35% (HR 3.6, 95% CI 1.6-8.1; p < 0.01) and use of positive inotropic agents (HR 2.2, 95% CI 1.0-4.8; p 0.04) as independent predictors of the adverse outcome. CONCLUSION: Rates of in-hospital events and short- as well as long-term mortality were significantly higher in TTS patients receiving catecholamine support as compared to the other study-patients. These results need further evaluation in pre-clinical and clinical trials to determine if external catecholamines contribute to an adverse clinical outcome already compromised by the initial insult.

Impact of Acute Cardiac Complications After Subarachnoid Hemorrhage on Long-Term Mortality and Cardiovascular Events.

BACKGROUND: Cardiac complications frequently occur after subarachnoid hemorrhage (SAH) and are associated with an increased risk of neurological complications and poor outcomes. The aim of this study was to evaluate the impact of acute cardiac complications after SAH on long-term mortality and cardiovascular events. METHODS: All patients admitted to our Neuro intensive care unit with verified SAH from January 2010 to April 2015, and electrocardiogram, echocardiogram, and troponin T or NTproBNP data obtained within 72 h of admission were included in the study. Mortality data were obtained from the Swedish population register. Data regarding cause of death and hospitalization for cardiovascular events were obtained from the Swedish Board of Health and Welfare. RESULTS: A total of 455 patients were included in the study analysis. There were 102 deaths during the study period. Cardiac troponin release (HR 1.08, CI 1.02-1.15 per 100 ng/l, p = 0.019), NTproBNP (HR 1.05, CI 1.01-1.09 per 1000 ng/l, p = 0.018), and ST-T abnormalities (HR 1.53, CI 1.02-2.29, p = 0.040) were independently associated with an increased risk of death. However, these associations were significant only during the first 3 months after the hemorrhage. Cardiac events were observed in 25 patients, and cerebrovascular events were observed in 62 patients during the study period. ST-T abnormalities were independently associated with an increased risk of cardiac events (HR 5.52, CI 2.07-14.7, p < 0.001), and stress cardiomyopathy was independently associated with an increased risk of cerebrovascular events (HR 3.65, CI 1.55-8.58, p = 0.003). CONCLUSION: Cardiac complications after SAH are associated with an increased risk of short-term death. Patients with electrocardiogram abnormalities and stress cardiomyopathy need appropriate follow-up for the identification of cardiac disease or risk factors for cardiovascular disease.

Impact and management of left ventricular function on the prognosis of Takotsubo syndrome.

BACKGROUND: Early research has proposed that patients with Takotsubo syndrome (TTS) could have a higher mortality rate than the general population. Our study was conducted to determine the short- and long-term outcome of TTS patients associated with a significantly compromised left ventricular function on hospital admission. MATERIALS AND METHODS: Our institutional database constituted a collective of 112 patients diagnosed with TTS between 2003 and 2015. The patients were classified into two groups based on the left ventricular ejection fraction (LVEF), with those presenting with a LVEF > 35% on admission categorized into one group (n = 65, 58%) and those presenting with LVEF ≤ 35% (n=47, 42%) categorized into another group. The endpoint was the all-cause of mortality over a mean follow-up of 1529 ± 1121 days. RESULTS: Preliminary results indicated that patients with an EF ≤ 35% had a significantly greater risk of developing life-threatening arrhythmias, and were much more likely to suffer from cardiogenic shock. Patients often required varying forms of mechanical respiratory support. The in-hospital mortality, 30-day mortality, 1-year mortality and ongoing long-term mortality was significantly higher in TTS patients with an EF ≤ 35%. In a multivariate Cox regression analysis, an EF ≤ 35% (HR 3·3, 95% CI: 1·2-9·2, P < 0·05) was identified as a strong independent predictor of the primary endpoint. CONCLUSIONS: In-hospital events as well as short- and long-term mortality rates among TTS patients diagnosed with a significantly reduced LVEF on admission were significantly higher. There is an urgent need for randomized trials, which could help define uniform clinical management strategies for high risk TTS patients.

Impact of concomitant atrial fibrillation on the prognosis of Takotsubo cardiomyopathy.

AIMS: Previous studies revealed that patients with Takotsubo cardiomyopathy (TTC) have a higher mortality rate than the general population. Supraventricular tachycardia is a well-known complication of TTC. This study was performed to determine the short- and long-term prognostic impact of atrial fibrillation associated with TTC patients. METHODS AND RESULTS: Our institutional database constituted a collective of 114 patients diagnosed with TTC from 2003 to 2015. The patients were divided into two groups according to the presence (n = 21, 18.4%) or absence (n = 93, 81.5%) of atrial fibrillation. The endpoint was a composite of in-hospital events (thromboembolic events and life-threatening arrhythmias), all-cause mortality, rehospitalization due to heart failure, stroke, and the recurrence of TTC. The in-hospital mortality, 30-day mortality, and long-term mortality were significantly higher in the atrial fibrillation group. Kaplan-Meier analysis indicated a significantly lower event-free survival rate over a mean follow-up of 3 years in the atrial fibrillation group than that in the non-atrial fibrillation group (log-rank, P < 0.01). In a multivariate cox regression analysis, atrial fibrillation (hazard ratio, HR 2.3, 95% confidence interval, CI: 1.1-4.9, P < 0.05) and EF ≤ 35% (HR 2.0, 95% CI: 1.1-3.8, P < 0.05) were the only independent predictors of a primary endpoint. CONCLUSION: Rates of in-hospital events and short- as well as long-term mortality were significantly higher in TTC patients suffering from atrial fibrillation compared with patients without atrial fibrillation.

Evaluation of therapy management and outcome in Takotsubo syndrome.

BACKGROUND: To date there is no validated evidence for standardized treatment of patients with Takotsubo syndrome (TTS). Medication therapy after final TTS diagnosis remains unclear. Previous data on patient outcome is ambivalent. Aim of this study was to evaluate medication therapy in TTS and to analyze patient outcome. METHODS: Within an observational retrospective cohort study we analyzed our medical records and included 72 patients with TTS that underwent cardiovascular magnetic resonance imaging (CMR) after a median of 2 days interquartile range (IQR 1-3.5). We investigated medication therapy at discharge. Medication implementation and major adverse clinical events (MACE) were prospectively evaluated after a median follow-up of 24 months (IQR 6-43). Left ventricular function, myocardial oedema and late gadolinium enhancement were analyzed in a CMR follow-up if available. RESULTS: Antithrombotic therapy was recommended in 69 (96%) patients including different combinations. Antiplatelet monotherapy was prescribed in 28 (39%) patients. Dual antiplatelet therapy was recommended in 29 (40%) patients. Length of therapy duration varied from one to twelve months. Only in one case oral anticoagulation was prescribed due to apical ballooning with a left ventricular ejection fraction <30%. In all other cases oral anticoagulation was recommended due to other indications. ß-adrenoceptor antagonists and ACE inhibitors were recommended in 63 (88%), mineralocorticoid receptor antagonists were prescribed in 31 (43%) patients. After a median of 2 months (IQR 1.3-2.9) left ventricular function significantly recovered (49.1% ± 10.1 vs. 64.1% ± 5.7, P < 0.001) and myocardial oedema significantly decreased (13.5 ± 11.3 vs. 0.6% ± 2.4, P = <0.001) in the CMR follow-up. The 30-day mortality was 1%. MACE rate after 24 months was 12%. CONCLUSION: Although therapy guidelines for TTS currently do not exist, we found that the majority of patients were treated with antithrombotic and heart failure therapy for up to twelve months. Left ventricular function and myocardial oedema recovered rapidly within the first two months. Outcome analysis showed a low bleeding rate and a high short-term survival. Therefore, TTS patients might benefit from antithrombotic and heart failure therapy at least for the first two months.

Seasonal variation in patient characteristics and in-hospital outcomes of Takotsubo syndrome: a nationwide retrospective cohort study in Japan.

Although there is reportedly seasonal variation in the occurrence of Takotsubo syndrome (TTS), it is unknown whether there is a relationship between season and patient characteristics, or whether season influences outcomes. Using the Diagnosis Procedure Combination database in Japan, we retrospectively identified 4306 patients (mean age 73.6 years) hospitalized with TTS between January 2011 and December 2013. We divided patients into four groups according to season of admission [n = 914, Spring (March-May); n = 1243, Summer (June-August); n = 1245, Autumn (September-November); n = 904, Winter (December-February)]. The outcomes were in-hospital mortality and cardiovascular complications. We compared patient backgrounds and outcomes across seasons and estimated the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for outcomes in logistic regression analyses adjusted for multiple propensity scores. Although there was no significant difference in age across seasons, the proportion of males differed significantly (from 18.5% in autumn to 23.9% in winter; p = 0.016). The incidence of psychiatric disease (from 4.9% in spring to 7.9% in summer; p = 0.025) and sepsis (from 0.8% in winter to 2.6% in summer; p = 0.019) also differed significantly with season. In-hospital mortality was not significantly influenced by season (p = 0.377): spring, 5.1%; summer, 6.0%; autumn, 4.6%; winter, 6.0%. However, in-hospital mortality ranged widely across months from 3.0% in September to 7.5% in April. The incidence of ventricular tachycardia/fibrillation was significantly different (p = 0.038): spring, 2.2% (reference); summer, 3.3% (aOR 1.46, 95% CI 0.84-2.51); autumn, 2.7% (aOR 1.27, 95% CI 0.72-2.22); winter, 4.4% (aOR 1.92, 95% CI 1.11-3.33). Although season did not appear to influence the in-hospital mortality of TTS, monthly variation may exist in the risk of death in patients with TTS. There were significant seasonal variations in the proportions of males, patients with psychiatric disease or sepsis, and the incidence of ventricular arrhythmias among patients with TTS.

Takotsubo syndrome in hemodynamically unstable patients admitted to the intensive care unit - a retrospective study.

INTRODUCTION: Takotsubo syndrome (TS) is an acute cardiac condition that is often triggered by critical illness but that has rarely been studied in the intensive care unit (ICU) setting. The aim of this study was to (i) estimate the incidence of TS in a hemodynamically unstable ICU-population; (ii) identify predictors of TS in this population; (iii) study the impact of TS on prognosis and course of hospitalization. METHODS: Medical records from all patients admitted to our general ICU from 2012 to 2015 were analyzed. TS was defined as having transient regional wall motion abnormalities (RWMA) with a typical pattern not attributable to a history of coronary artery disease or acute coronary syndromes. RESULTS: Out of 6470 patients admitted to the ICU, echocardiography due to hemodynamic instability was performed in 1051 patients; 467 had LV dysfunction and 59 fulfilled TS criteria. Patients with TS had higher SAPS 3 scores on admission than patients with normal LV function. Septic shock, cardiac arrest, cerebral mass lesion, female sex and low pH were independently associated with TS on admission. Patients with TS needed more ICU resources measured by higher NEMS scores and longer ICU-stay. Crude mortality was higher in TS patients (32%) vs the ICU-population (20%, P = 0.020), but there were no differences in a SAPS 3 adjusted analysis. CONCLUSION: TS was not an uncommon cause of LV dysfunction in hemodynamically unstable ICU-patients. Furthermore, TS was associated with a more complex disease. TS is a complication to take in consideration in the critically ill.

Predictive Value of QRS Duration at Admission for In-Hospital Clinical Outcome of Takotsubo Cardiomyopathy.

BACKGROUND: Prolonged QRS duration (pQRSd) on electrocardiogram (ECG) is a strong predictor of poor outcome in heart failure, myocardial infarction, and myocarditis, but it is unclear whether pQRSd also predicts poor outcomes of takotsubo cardiomyopathy (TC).Methods and Results:Between 1 January 2010 and 31 December 2012, we retrospectively enrolled 299 patients with TC (mean age, 73.5±11.7 years; 21.4% male) from the Tokyo CCU Network database, which consists of 71 cardiovascular centers in the metropolitan area. In-hospital clinical outcomes were compared between patients with pQRSd on admission ECG (QRS ≥120 ms; n=34) and those with normal QRS duration (<120 ms; n=265). The in-hospital mortality rate for pQRSd was significantly higher than that for normal QRS duration (23.5% vs. 3.8%, P<0.001). Similarly, prevalence of ventilator use (38.2% vs. 11.4%, P<0.001), ventricular tachycardia or fibrillation (14.7% vs. 1.5%, P<0.001), and circulatory failure requiring catecholamine or cardiopulmonary supportive devices (41.2% vs. 14.0%, P<0.001) was significantly higher in the pQRSd group. On multivariate logistic regression analysis, pQRSd was an independent predictor for both in-hospital mortality (OR, 5.06; 95% CI: 1.79-14.30, P=0.002) and cardiac death (OR, 7.34; 95% CI: 1.33-40.51, P=0.02). CONCLUSIONS: TC with pQRSd is associated with poor in-hospital clinical outcome. Aggressive intervention may be required to prevent severe complications in these patients.

QT Prolongation and Clinical Outcomes in Patients with Takotsubo Cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TCM) has been associated with repolarization abnormalities including QT prolongation and acquired long QT syndrome. However, the association between QT prolongation and clinical outcomes in patients with TCM remains unclear. The aim of this study is to examine the association between QT prolongation and ventricular arrhythmias, cardiogenic shock, and death in patients with TCM. METHODS: Forty-six patients with TCM met our inclusion criteria in an ongoing prospective cohort database from 2010 to May 2015. We assigned the patients to a long QT group or a normal QT group, and created a composite outcome consisting of ventricular arrhythmias, cardiogenic shock, or death. RESULTS: The mean age of the participants was 59.7 ± 16 years, 67% were women, and 63% had hypertension. Median follow-up time was 3.1 years (interquartile range: 2.0-3.8), with a total of 133.8 person-years. The mean left ventricular ejection fraction at diagnosis was 27.2% ± 1.4%. The mean QTc on diagnosis was 484 ms ± 10.2 ms for men, and 488 ms ± 8.6 ms for women. The long QT group had a 4.1-times higher odds of having the composite clinical outcome as compared to the normal QT group (95% confidence interval: 1.1, 16.1, P = 0.04) after adjusting for age and race in logistic regression. CONCLUSION: Patients with TCM who have a long QT interval or develop acquired long QT syndrome due to TCM may be more likely to be intubated; require vasopressors; and develop shock, ventricular arrhythmias, and death than those with a normal QT interval.